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bioRxiv · 10.1101/2023.09.22.558941

Spine apparatus modulates Ca2+ in spines through spatial localization of sources and sinks

Hernandez Mesa, M.·Garcia, G. C.·Hoerndli, F.·McCabe, K. J.·Rangamani, P.
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Abstract

Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work, we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca2+ in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca2+ dynamics differently from spines without ER through a combination of geometry and receptor localization. 1 HighlightsO_LIRyR opening in dendritic spine ER is location dependent and spine geometry dependent. C_LIO_LICa2+ buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated. C_LIO_LIRyRs located towards the ER neck allow for more Ca2+ to reach the dendrites. C_LIO_LIRyRs located towards the spine head are favorable for increased Ca2+ in spines. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/558941v1_fig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a2aa64org.highwire.dtl.DTLVardef@60a7c5org.highwire.dtl.DTLVardef@1a68303org.highwire.dtl.DTLVardef@e3743f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Graphical abstract. Factors governing the dynamics of Ca2+ in dendritic spines include plasma membrane geometry, RyR distribution and ER laminarity. C_FIG

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Hernandez Mesa, M., Garcia, G. C., Hoerndli, F., McCabe, K. J., Rangamani, P.. 2023-09-22. Spine apparatus modulates Ca2+ in spines through spatial localization of sources and sinks. https://doi.org/10.1101/2023.09.22.558941

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